The membranes of mouse neuroblastoma cells undergo a dramatic increase in resistance to lipid peroxidation during differentiation. A sensitive, single-phase assay for antioxidant activity was developed in this laboratory in order to test the hypothesis that a lipid-soluble antioxidant was generated by these cells. Studies on lipid extracts revealed several antioxidant fractions but none of these increased in potency during neuroblastoma differentiation. Thus, the increased membrane resistance did not appear to be due to an antioxidant. In addition, studies on the lipid composition of differentiated and undifferentiated neuroblastoma cells have failed to reveal changes which could explain the increase in resistance. The hypotheses that differences in membrane structure can account for the increased resistance is presently under investigation. Particularly interesting is the possibility that differentiated membranes might exhibit resistance to lipid peroxidation after detergent-solubilization and reconstitution.